Search Results (900)

Vitamin D is the only vitamin that is conditionally essential, as it is synthesized from precursors after UV light exposure, whilst also being obtained from the diet. It has numerous health benefits, with deficiency becoming a major concern globally, such that dietary supplementation has more recently achieved vital importance to maintain satisfactory levels. In recent years, measurements made from blood have, therefore, become critical to determine the status of vitamin D levels in individuals and the larger population. Tests for vitamin D have routinely relied on laboratory analysis with sophisticated equipment, often being slow and costly, whilst rapid immunoassays have suffered from poor specificity and sensitivity. Here, we have evaluated a new rapid immunoassay test on the market (Rapi-D & IgLoo) to quickly and accurately measure vitamin D levels in small capillary blood specimens and compared this to measurements made using the standard laboratory method of liquid chromatography and mass spectrometry. Our results show that vitamin D can be measured very quickly and over a broad range using the new method, as well as correlate relatively well with standard laboratory testing; however, it cannot be fully relied upon currently to accurately diagnose deficiency or sufficiency in individuals. Our statistical and comparative analyses find that the rapid immunoassay with digital quantification significantly overestimates vitamin D levels, leading to diminished diagnosis of vitamin D deficiency. The speed and simplicity of the rapid method will likely provide advantages in various healthcare settings; however, further calibration of this rapid method and testing parameters for improving quantification of vitamin D from capillary blood specimens is required before integration of it into clinical decision-making pathways. Full article

Objective: This study aimed to determine the possibility of creating a new animal model in which diabetic retinopathy (DR) progresses due to hypertension caused by salt loading. Methods: Male Spontaneously Diabetic Torii (SDT) fatty rats were divided into two groups: one group received 0.3% saline water starting at 8 weeks of age for a duration of 16 weeks (salt SDT fatty group), while the control group was provided with tap water (SDT fatty group). In addition, Sprague-Dawley (SD) rats receiving tap water served as normal controls. Retinal function was assessed by electroretinography (ERG) at 8 and 24 weeks of age. At 24 weeks, following perfusion with fluorescein dextran, the eyes were enucleated, and retinal flat mounts were prepared for vascular evaluation. Retinal thickness and the number of retinal folds were assessed histologically, and ultrastructural changes in the retina were examined using transmission electron microscopy. Results: Saline administration did not lead to significant changes in food consumption or body weight among the groups. In the salt SDT fatty group, blood pressure was significantly elevated, while blood glucose levels showed a slight reduction. ERG analysis showed that the amplitude of oscillatory potential (OP)1 waves was suppressed, and the latencies of OP3, OP4, and OP5 waves were prolonged. Although no significant changes were noted in retinal thickness or the number of retinal folds, thickening of the retinal capillary basement membrane was evident in the salt SDT fatty group. Conclusions: Hypertension induced by 0.3% saline promotes DR progression in SDT fatty rats. This model may help clarify the role of hypertension in DR. Full article

Background/Objectives: Conventional blood collection can be challenging in a non-clinical or home-based setting. In response, vacuum-assisted lancing devices for capillary blood collection (typically from the upper arm) have gained popularity to broaden access to diagnostic testing. However, these devices are often costly relative to the reimbursement rate for common laboratory testing panels. This study describes the design and evaluation of Comfort Draw™, a simplified and economical vacuum-assisted capillary blood collection device. Methods: Comfort Draw™ was evaluated by 12 participants in a preliminary study and by 42 participants in a follow-up study. Metrics assessed included the following: vacuum pressure of the device, skin temperature generated by the Comfort Draw prep warmer, blood collection volume, and analytical accuracy (for 19 common serum-based analytes). Results: Acceptable blood volume (>400 µL) and serum volume (>100 µL) were collected by Comfort Draw in 85.5% and 95.1% of cases, respectively. Seventeen of the nineteen analytes examined were within CLIA acceptance limits compared to matched venous samples. Self-reported pain scores associated with Comfort Draw collection averaged 0.39 on a scale from 0 to 10. Conclusions: In this preliminary clinical study, Comfort Draw was found to be a valid and relatively painless method for collecting capillary blood specimens. The device’s simple design and lower cost could enable broader applications compared to more complex alternative capillary blood collection devices. Full article

Lower respiratory tract infections remain a leading cause of morbidity and mortality among Intensive Care Unit patients, with severe cases often progressing to acute respiratory distress syndrome (ARDS). This life-threatening syndrome results from alveolar–capillary membrane injury, causing refractory hypoxemia and respiratory failure. Early detection and management are critical to treat the underlying cause, provide protective lung ventilation, and, eventually, improve patient outcomes. The 2012 Berlin definition standardized ARDS diagnosis but excluded patients on non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) modalities, which are increasingly used, especially after the COVID-19 pandemic. By excluding these patients, diagnostic delays can occur, risking the progression of lung injury despite ongoing support. Indeed, sustained, vigorous respiratory efforts under non-invasive modalities carry significant potential for patient self-inflicted lung injury (P-SILI), underscoring the need to broaden diagnostic criteria to encompass these increasingly common therapies. Recent proposals expand ARDS criteria to include NIV and HFNCs, lung ultrasound, and the SpO₂/FiO₂ ratio adaptations designed to improve diagnosis in resource-limited settings lacking arterial blood gases or advanced imaging. However, broader criteria risk overdiagnosis and create challenges in distinguishing ARDS from other causes of acute hypoxemic failure. Furthermore, inter-observer variability in imaging interpretation and inconsistencies in oxygenation assessment, particularly when relying on non-invasive measurements, may compromise diagnostic reliability. To overcome these limitations, a more nuanced diagnostic framework is needed—one that incorporates individualized therapeutic strategies, emphasizes lung-protective ventilation, and integrates advanced physiological or biomarker-based indicators like IL-6, IL-8, and IFN-γ, which are associated with worse outcomes. Such an approach has the potential to improve patient stratification, enable more targeted interventions, and ultimately support the design and conduct of more effective interventional studies. Full article

Background: Citrinin (CIT) is a mycotoxin produced by various fungi contaminating stored cereals and fruits. While biomonitoring and food occurrence data indicate widespread exposure, its public health risks remain unclear due to the lack of human toxicokinetic (TK) data. Methods: A UHPLC-MS/MS method was validated for CIT quantification in capillary blood (VAMS Mitra^® tips), feces, and urine obtaining LLOQs ≤ 0.05 ng/mL. A human TK study was conducted following a single oral bolus of 200 ng/kg bw CIT. Individual capillary blood (VAMS Mitra^® tips), feces, and urine samples were collected for 48 h after exposure. Samples were analyzed to determine CIT’s TK profile. Results: TK modeling was performed using a multi-compartmental structure with a hierarchical Bayesian population approach, allowing robust parameter estimation despite the lack of standards for CIT metabolites. Conclusions: The derived TK parameters align with preliminary human data and significantly advance CIT exposure assessment via biomonitoring. A human inter-individual toxicokinetic variability (HK_AF) of 1.92 was calculated based on the derived AUC, indicating that EFSA’s current default uncertainty factor for TK variability is adequately protective for at least 95% of the population. Full article

Background: Crystalline glucosamine sulfate (cGS) claims to be a stabilized form of glucosamine sulfate with a defined crystalline structure intended to enhance chemical stability. It is proposed to offer pharmacokinetic advantages over regular glucosamine sulfate (rGS) which is stabilized with potassium or sodium chloride. However, comparative human bioavailability data are limited. Since both forms dissociate in gastric fluid into constituent ions, the impact of cGS formulation on absorption remains uncertain. This pilot study aimed to compare the bioavailability of cGS and rGS using a randomized, double-blind, crossover design. Methods: Ten healthy adults received a single 1500 mg oral dose of either cGS or rGS with a 7-day washout between interventions. Capillary blood samples were collected over 24 h. Glucosamine and its metabolite concentrations were quantified by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS), and pharmacokinetic parameters—including maximum concentration (C_max), time to reach C_max (T_max), and area under the curve (AUC)—were calculated. Results: Mean AUC_0–24, C_max, T_max, and T_½ values for glucosamine and glucosamine-6-sulfate (GlcN-6-S) were comparable between cGS and rGS. Although the AUC_0–24 for glucosamine was modestly higher with rGS (18,300 ng·h/mL) than with cGS (12,900 ng·h/mL), the difference was not statistically significant (p = 0.136). GlcN-6-S exposure was also similar between formulations (rGS: 50,700 ng·h/mL; cGS: 50,600 ng·h/mL), with a geometric mean ratio of 1.39, a delayed T_max (6–8 h) and longer half-life, consistent with its role as a downstream metabolite. N-acetylglucosamine levels remained stable, indicating potential homeostatic regulation. Conclusions: This pilot study found no significant pharmacokinetic advantage of cGS over rGS. These preliminary findings challenge claims of cGS’ pharmacokinetic superiority, although the small sample size limits definitive conclusions. Larger, adequately powered studies are needed to confirm these results. Full article

Plasmodium falciparum malaria remains a major cause of morbidity and mortality, particularly in endemic regions. We report the case of a 21-year-old male with recent travel to an endemic area (Guapi, Colombia), who presented with febrile symptoms, severe respiratory distress, and oxygen saturation below 75%, necessitating orotracheal intubation. During the procedure, he developed pulseless electrical activity cardiac arrest, achieving return of spontaneous circulation after advanced resuscitation. Diagnosis was confirmed by thick blood smear, demonstrating P. falciparum infection. The patient progressed to multiorgan failure, including acute respiratory distress syndrome with capillary leak pulmonary edema, refractory distributive shock, acute kidney injury with severe hyperkalemia, and consumptive thrombocytopenia. Management included invasive mechanical ventilation, vasopressor support, sedation-analgesia, neuromuscular blockade, methylene blue, unsuccessful hemodialysis due to hemorrhagic complications, and platelet transfusions. Despite these interventions, the patient experienced a second cardiac arrest and died. This case highlights the severity and rapid progression of severe malaria with multisystem involvement, underscoring the critical importance of early diagnosis and intensive multidisciplinary management. It also emphasizes the need for preventive strategies for travelers to endemic areas and the development of clinical protocols to improve outcomes in complicated malaria. Full article

Everolimus (EVE), an mTOR inhibitor, is widely used in solid organ transplantation (SOT) because of its immunosuppressive properties. Due to its narrow therapeutic window and significant pharmacokinetic variability, therapeutic drug monitoring (TDM) is essential for achieving optimal outcomes. We developed and thoroughly validated a robust LC-MS/MS method to measure EVE levels in venous whole blood (WB) and capillary blood collected using two microsampling devices: Mitra™ (volumetric absorptive microsampling, VAMS) and Capitainer^® (quantitative dried blood spot, qDBS). The validation followed EMA and IATDMCT guidelines, assessing linearity (1.27–64.80 ng/mL for WB and 0.50–60 ng/mL for VAMS/qDBS), as well as selectivity, accuracy, precision, matrix effects, recovery, stability, and incurred sample reanalysis. Clinical validation involved 66 matched samples from 33 adult SOT recipients. The method demonstrated high accuracy and precision across all matrices, with no significant carryover or matrix interference. Statistical analysis using Passing–Bablok regression and Bland–Altman plots showed excellent agreement between the microsampling methods and the venous reference. Hematocrit effects were tested both in laboratory conditions and on clinical samples and were found to be negligible. This study provides the first comprehensive analytical and clinical validation of the Mitra and Capitainer devices for EVE monitoring. The validated LC-MS/MS microsampling method supports decentralized, patient-centred TDM, offering a reliable alternative to conventional blood sampling in transplant care. Full article

Background/Objectives: Diabetic macular edema (DME) is the primary cause of vision loss in people with diabetes, and if untreated, it can result in irreversible macular damage. Both fluorescein angiography (FA), the gold standard, and optical coherence tomography angiography (OCTA) are used for evaluation of this disease. The objective of this study was to compare the diagnostic value of both. Methods: We conducted a comparative analysis of 98 patients aged 18–80 years with significant DME and best-corrected visual acuity ≥0.1 according to the Snellen chart. Participants underwent glycated hemoglobin blood test (HbA1c) and ophthalmological examinations, including OCTA and FA. OCTA 3 × 3 mm scans of superficial (SCP) and deep capillary plexus (DCP) along with FA scans were exported to the Gimp computer program. Size of the foveal avascular zone (FAZ), the number of visible microaneurysms (MAs), and ETDRS report number 11 classification of the images were assessed. Results: FAZ size differed significantly in superficial plexus (0.41 mm²), deep plexus (0.43 mm²) OCTA, and FA (0.38 mm²) (p < 0.001). FAZ size in DCP OCTA closely correlated with that of FA (τ = 0.79, p < 0.001). The total number of MAs visualized in the OCTA was significantly lower than in FA (p < 0.001). ETDRS classification of scans revealed that the level of consistency between the examinations was moderate to very strong. Conclusions: OCTA may be useful in evaluating macular ischemia. It is less sensitive in detecting MAs in DME eyes. FAZ has sharper boundaries and is larger when measured in OCTA. Poor glycemic control results in higher incidence of MAs in macula. Full article

In healthy humans, insulin at physiological concentrations exerts acute vasodilatory actions on both resistance and terminal arterioles, leading, respectively, to increased total blood flow and the microvascular network volume being perfused. The process of increasing capillary network volume is frequently referred to as “capillary recruitment”. Together these two vascular actions of insulin enhance the delivery of oxygen, nutrients, and insulin itself to tissues. Both processes are diminished by insulin resistance. Here we examined interactions between insulin’s acute (within 2 h) actions on blood pressure (both central and peripheral) and on capillary recruitment in healthy controls and in four distinct groups of people with heightened cardio-metabolic disease (CMD) risk: individuals with obesity, metabolic syndrome, and type 1 or type 2 diabetes. Insulin increased microvascular blood volume (MBV) more effectively in controls than in each of the four CMD risk groups (p < 0.001). Conversely, insulin lowered both central and peripheral systolic pressure (p < 0.05 or less) in each of the CMD risk groups but not in the controls. The insulin-induced blood pressure decrements were greater in the metabolic syndrome, type 2 diabetes, and obesity groups (p < 0.05 or less) than in the controls. The greater blood pressure declines likely reflect decreased sympathetic baroreceptor reflex tone. These effects on blood pressure combined with the diminished dilation of terminal arterioles due to microvascular insulin resistance in the CMD risk subjects led to decreased distal microvascular perfusion as evidenced by changes in MBV. These findings highlight the complex interplay between insulin’s actions on resistance and terminal arterioles in individuals with a high CMD risk, underscoring the importance of addressing microvascular dysfunction in these conditions. Full article

The mechanical stability and deformability of erythrocytes are vital for their function as they traverse capillaries, where shear stress can reach up to 10 Pa under physiological conditions. Human serum albumin (HSA) is known to help maintain erythrocyte stability by influencing cell shape, membrane integrity, and resistance to hemolysis. However, the precise mechanisms by which albumin exerts these effects remain debated, with some studies indicating a stabilizing role and others suggesting the opposite. This review highlights that under high shear rates, albumin molecules may undergo unfolding due to normal stress differences. Such structural changes can significantly alter albumin’s interactions with the erythrocyte membrane, thereby affecting cell mechanical stability. We discuss two potential scenarios explaining how albumin influences erythrocyte mechanics under shear stress, considering both the viscoelastic properties of blood and those of the erythrocyte membrane. Based on theoretical analyses and experimental evidence from the literature, we propose that albumin’s effect on erythrocyte mechanical stability depends on (i) the transition between unfolded and folded states of the protein and (ii) the impact of shear stress on the erythrocyte membrane’s ζ-potential. Understanding these factors is essential for elucidating the complex relationship between albumin and erythrocyte mechanics in physiological and pathological conditions. Full article

Syphilis, which is caused by Treponema pallidum, remains one of the most common congenital infection worldwide and has tremendous consequences for the mother and her developing foetus if left untreated. The complexity of the exposure to this pathogen extends beyond the well-established clinical manifestations, as it can profoundly affect placental histomorphology. This study aimed to compare T. pallidum-exposed placental villi structures with healthy placentae at term to evaluate the histomorphological differences using stereology. In this case-control study conducted at term (38 weeks ± 2 weeks), 78 placentae were collected from the hospital delivery suites, comprising 39 cases (T. pallidum-exposed) and 39 controls (non-exposed), who were gestational age-matched with other potential confounders excluded. Blood samples from the umbilical vein and placental basal plate were tested for syphilis, using rapid diagnostic test (RDT) kits for T. pallidum (TP) antibodies (IgG and IgM) to classify placentae as exposed to T. pallidum (cases) and non-exposed (controls). Tissue sections were prepared and stained with haematoxylin and eosin, and the mean volume densities of syncytial knots, foetal capillaries, syncytial denuded areas, and intervillous spaces were estimated using stereological methods. Statistical analysis was performed to compare the mean values between the case and control groups. Stereological assessment revealed significant differences between the T. pallidum-exposed and non-exposed groups with regard to syncytial knots (p < 0.0001), syncytial denudation (p < 0.0001), and foetal capillaries (p < 0.0001), but no significant difference in the intervillous space was found (p = 0.1592). Therefore, our study shows, for the first time, that the histomorphology of human placental villi appears to be altered by exposure to T. pallidum. It will, therefore, be interesting to determine whether these changes in the placental villi translate into long-term effects on the baby. Full article

Peripheral circulatory failure refers to a condition in which the blood flow through superficial capillaries is markedly reduced or completely occluded. In clinical practice, nurses strictly adhere to regular repositioning protocols to prevent peripheral circulatory failure, during which the skin condition is evaluated visually. In this study, skin colour changes resulting from pressure application were continuously captured using a camera, and supervised machine learning was employed to classify the data into two categories: before and after pressure. The evaluation of practical colour space components revealed that the h component of the JCh colour space demonstrated the highest discriminative performance (Area Under the Curve (AUC) = 0.88), followed by the a* component of the CIELAB colour space (AUC = 0.84) and the H component of the HSV colour space (AUC = 0.83). These findings demonstrate that it is feasible to quantitatively evaluate skin colour changes associated with pressure, suggesting that this approach can serve as a valuable indicator for dimensionality reduction in feature extraction for machine learning and is potentially an effective method for preventing pressure-induced skin injuries. Full article

Coronary microvascular obstruction and dysfunction (CMVO) frequently arise following primary percutaneous coronary intervention (PCI), particularly in individuals with myocardial infarction. Despite the restoration of epicardial blood flow, microvascular perfusion might still be compromised, resulting in negative clinical outcomes. CMVO is a complex condition resulting from a combination of ischemia, distal thrombotic embolization, reperfusion injury, and individual susceptibilities such as inflammation and endothelial dysfunction. The pathophysiological features of this condition include microvascular spasm, endothelial swelling, capillary plugging by leukocytes and platelets, and oxidative stress. Traditional angiographic assessments, such as Thrombolysis in Myocardial Infarction (TIMI) flow grade and myocardial blush grade, have limited sensitivity. Cardiac magnetic resonance imaging (CMR) stands as the gold standard for identifying CMVO, while the index of microvascular resistance (IMR) is a promising invasive option. Treatment approaches involve powerful antiplatelet drugs, anticoagulants, and supersaturated oxygen, yet no treatment has been definitively shown to reverse established CMVO. CMVO remains a significant therapeutic challenge in coronary artery disease management. Enhancing the comprehension of its core mechanisms is vital for the development of more effective and personalized treatment strategies. Full article

Arteriovenous malformations (AVMs) are congenital vascular anomalies defined by abnormal direct connections between arteries and veins due to their complex structure or endovascular approaches. Pharmacological strategies targeting the underlying molecular mechanisms are thus gaining increasing attention in an effort to determine the mechanism involved in AVM regulation. In this study, we examined 30 human tissue samples, comprising 10 vascular samples, 10 human fibroblasts derived from AVM tissue, and 10 vascular samples derived from healthy individuals. The pharmacological agents thalidomide, U0126, and rapamycin were applied to the isolated endothelial cells (ECs). The pharmacological treatments reduced the proliferation of AVM ECs and downregulated miR-135b-5p, a biomarker associated with AVMs. The expression levels of angiogenesis-related genes, including VEGF, ANG2, FSTL1, and MARCKS, decreased; in comparison, CSPG4, a gene related to capillary networks, was upregulated. Following analysis of these findings, skin samples from 10 AVM patients were reprogrammed into induced pluripotent stem cells (iPSCs) to generate AVM blood vessel organoids. Treatment of these AVM blood vessel organoids with thalidomide, U0126, and rapamycin resulted in a reduction in the expression of the EC markers CD31 and α-SMA. The establishment of AVM blood vessel organoids offers a physiologically relevant in vitro model for disease characterization and drug screening. The authors of future studies should aim to refine this model using advanced techniques, such as microfluidic systems, to more efficiently replicate AVMs’ pathology and support the development of personalized therapies. Full article